Allergy typically is diagnosed using a battery of tests, of which skin tests are most prevalent. An allergy may be diagnosed by testing for skin reactivity on contact with the allergen. A positive result generally presents itself as a local inflammatory skin reaction, which is either moderate in the form of erythema (first clinical element of the inflammatory reaction), or in the form of a papula also indicating the presence of local edema (another component of the inflammatory reaction).
Skin reactivity also may result in response to contact with an allergen other than a contact allergen, such as respiratory or food allergens. That skin reactivity is explained by the constant circulation of immunological elements in the blood, allowing lymphocytes sensitized by the allergens, which have entered the body via the respiratory or digestive tracts, to accumulate within the skin.
Several skin tests are currently known for detecting the sensitization state of an individual with respect to both contact allergens and respiratory and food allergens.
Among these, a test referred to as the “Prick Test” is particularly well-known. The Prick Test may be employed for all allergens capable of triggering an immediate skin reaction to food or respiratory allergens. During this test, a solution containing the allergen is deposited onto the skin, and then the allergen is brought into contact with the immunological elements by means of a stylet or needle, which is used to perforate the superficial part of the dermis that is located adjacent to the solution. The Prick Test is analyzed after half an hour after the allergen is brought into contact with the dermis. In other words, and as already mentioned, this test makes it possible to detect an immediate reaction, which is in general IgE-dependent, i.e. using a type-E immunoglobulin reactivity. The analysis is performed by comparing the reaction at the test site with a positive control site, such as an area exposed to a histamine, and a negative control site, such as an area exposed to physiological saline or the solvent used to dilute the allergens. One drawback of the Prick Test is that it is painful to the patient due to perforation of the dermis with the stylet or needle. Another drawback of the Prick Test is that it is useful only for assessing immediate reactivity. Performing such a test demands the presence of a specialized staff in order to act quickly in case of anaphylactic reaction. This is the reason why the prick test is gradually rejected.
It appears that a number of allergic reactions occur in a delayed or semi-delayed manner, for example within a period of several hours to several days. It has, moreover, been noted that simple contact between the skin and an allergen may cause the appearance of systemic reactions. It is therefore hypothesized that the allergen diffuses through the skin in such a way that it can trigger immediate reactions just as it can trigger delayed reactions.
Accordingly, it has been proposed to deposit an allergen on a support configured to be maintained in contact with the skin for an extended period, so as to allow the allergen to pass through the skin and thus to trigger a skin reaction. Two main types of test have been developed and are known generically as “patch tests”.
A first patch test is known under the name FINN CHAMBERS® (a registered trademark of Epitest Ltd. of Tuusula, Finland). It comprises an adhesive support to which are bonded small metal cupules approximately one centimeter in diameter and 2 to 3 millimeters in depth. These cupules receive a diluted allergen mixture deposited onto a cellulose pad supported within the cupule. The mixture is prepared extemporaneously from the native product or from allergens in suspension. The cellulose pad is placed at the bottom of the cupule and the cupule is attached to the patient's skin. The test is analyzed after 48 hours, after removing the material, cleaning the skin and waiting for a short period of time, approximately half an hour, to allow specific local phenomena, associated with the pressure of the edge of the cupule on the skin or with the presence of the adhesive, to disappear.
When using FINN CHAMBERS®, a positive reaction combines erythema, edema and a macular rash at the point of contact, which is compared with any reaction caused by a negative control (cellulose support simply dampened with water). The interpretation is generally easy, but the reaction is not precisely quantifiable. FINN CHAMBERS® may be used to test numerous categories of allergens, whether contact allergens or others. In particular, the allergen/cellulose mixture prepared extemporaneously can, for example, contain foods in order to search for a food allergy, pollen in order to search for a respiratory allergy, or a dye or a metal in order to search for a contact allergy.
While the foregoing method makes it possible to use allergens of infinite variety, it has the drawback of being difficult to use. Specifically, erroneous results may be obtained, for example, due to:                movement of the cellulose pad when the cupule is applied;        contamination of the allergenic mixture, if present in excess amounts, with allergens in neighboring cavities;        use of an allergen concentration that is too low to cause an allergic reaction; and/or        lack of standardization of test results due to variability in the amount of allergen employed from test to test.        
Moreover, if the test is used to detect several allergens, there is a risk of confusion during the interpretation, due to the fact that the allergens used cannot be pinpointed on the adhesive supports. In addition, this type of test requires use of allergens that are fresh or in suspension, and which must be solubilized or dispersed in a solvent extemporaneously, i.e. just before the test is applied to the skin.
All of the foregoing factors render results obtained using FINN CHAMBERS® random unless employed by highly trained personnel, thus limiting use of that systems to specialized centers. Consequently, routine use of the foregoing test routinely is limited, especially with respect to doctors' offices.
A patch similar to the FINN CHAMBERS® patch is available under the name LEUKOTEST® (a registered trademark of Cambridge Biotech Corp. of Worcester, Mass.). However, in this device PVC chambers are included in the adhesive support and not bonded to the adhesive support. The chambers contain cellulose pads which are not removable, but remain attached to the cupule. The test is prepared extemporaneously with ready-to-use allergens that are fresh or in suspension. It is easier to use than the FINN CHAMBERS®, but also presents many handling error risks. The following disadvantages are noted:                the lack of control of the amount of allergen introduced into each chamber;        the lack of indication concerning the nature of the allergens used on the plastic supports; and also        the need to have the allergens in a form suitable for deposition on the cellulose pads.        
Another type of patch is available under the name T.R.U.E. TEST® (a registered trademark of Mekos Laboratories of Hillerod, Denmark) and is described in U.S. Pat. No. 4,836,217 to Fischer. The T.R.U.E. TEST® eliminates the presence of the metal cupules, which it substitutes with a gel, into which the allergens are incorporated, the gel being applied directly on an adhesive strip. Only contact allergens can be incorporated into the gel. Thus, if the allergen is soluble in the solvent that is contained in the gel, then the allergen may be directly incorporated into the gel. On the other hand, if the allergen is insoluble, it is necessary to disperse it as homogeneously as possible directly into the gel. The main drawbacks of this type of patch are that is a gel substrate that may interact with the allergen. There can thus be no guarantee that the allergens will be maintained in their organic origin or reactogenic state of origin.
More particularly applied to the case of the allergens, it would be desirable to provide a patch that makes it possible to test all allergens and, in addition, ensures that organic allergens are maintained in their reactogenic state.
It also would be desirable to provide a ready-to-use patch, i.e. a patch which requires no extemporaneous preparation of the allergen prior to application of the patch to a patient or subject.
It further would be desirable to provide a patch capable of containing and delivering, on contact with the skin, a predetermined amount of biologically active substance, which is constant from one patch to another, thereby ensuring that the treatment or test is reliable and reproducible.